Feasibility and Safety of PD-1 Blockades Among Elderly Patients with Metastatic Esophageal Squamous Cell Carcinoma: A Real-World Study.

Objective: This study aimed to identify the effectiveness and safety of PD-1 blockades among elderly patients with metastatic esophageal squamous cell carcinoma (ESCC) clinically. Methods: A total of 78 elderly patients with previously treated metastatic ESCC aged ≥65 years who received PD-1 blockades monotherapy were included retrospectively. Demographic characteristics, therapeutic effectiveness and adverse reactions of the elderly patients who underwent PD-1 blockade therapy were recorded. Regular follow-up was conducted for all patients. The analysis aimed to identify potential risk factors for OS by examining the correlation between prognosis and subgroups based on baseline characteristics. Results: The median age of the 78 elderly patients was 73 years, ranging from 65 to 87 years. Among the 78 patients, 18 cases showed partial response, 26 cases had stable disease, 29 cases experienced progressive disease and 5 cases were not assessable for response, yielding an ORR of 23.1%, a DCR of 56.4%. The prognostic outcomes indicated that among the 78 patients with metastatic ESCC who received PD-1 blockades, the median PFS was 3.1 months [95% confidence interval (CI): 1.64-4.56], and the median OS was 10.9 months (95% CI: 6.02-15.78), 24-month OS rate was 22.7% (95% CI: 12.8-34.2%). In terms of the safety profile, among the 78 patients with metastatic ESCC during PD-1 blockades single-agent treatment, a total of 61 patients (78.2%) experienced any grade adverse reactions and the incidence of grade ≥3 adverse reactions were 20.5%. Briefly, the common adverse reactions manifested as fatigue (32.1%), gastrointestinal reaction (24.4%), diarrhea (19.2%), anemia (17.9%) and rash (16.7%). Overall tolerability of PD-1 blockade monotherapy in elderly patients with metastatic ESCC was acceptable and manageable. Conclusion: PD-1 blockades single agent demonstrated encouraging effectiveness and acceptable safety profile for elderly patients with previously treated metastatic ESCC in clinical practice. Prospective study should be performed to elucidate the conclusion in this study subsequently.

Hydroxyl-Amide Alkaloids from Pepper Roots: Potential Sources of Natural Antioxidants and Tyrosinase Inhibitors.

Pepper (Piper nigrum L.) is a widely used spice plant known for its fruits and roots, which serve as flavor enhancers in culinary applications and hold significant economic value. Despite the popularity of pepper fruits, their roots remain relatively understudied, with limited research conducted on their bioactive components. This study focused on discovering and separating the primary bioactive amide alkaloids found in pepper roots. The process involved using the antioxidant activity of crude fractions and the Global Natural Products Social Molecular Networking analysis platform. The process led to the discovery of 23 previously unknown hydroxyl-amide alkaloids. Notably, compounds 11, 12, and 14 showed excellent antioxidant activity, while compound 11 exhibited significant inhibitory effects on mushroom tyrosinase. Theoretical exploration of enzyme-ligand interactions was conducted through molecular docking and molecular dynamics simulation. The findings of this study highlight the potential of hydroxyl-amide alkaloids as antioxidant products and natural food preservatives in the pharmaceutical and food cosmetic industries.

Analysis of long non-coding RNA RMRP in the diagnosis and prognosis of coronary artery disease.

BACKGROUND: Long non-coding RNAs (lncRNAs) are abundant and closely related to the occurrence and development of human diseases. LncRNAs are known to play a key role in many cardiovascular diseases. The purpose of this study was to investigate the effect of the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP) on the degree of coronary artery lesions and prognosis in patients with coronary artery disease (CAD). METHODS: Patients who underwent coronary angiography (CAG) and dynamical-single photon emission computed tomography (D-SPECT) were selected as study subjects, and the results of CAG were reviewed, and the patients were grouped according to SYNTAX score. Evaluate the factors affecting SYNTAX scores. The follow-up analysis was conducted, and the endpoint events were major adverse cardiovascular events (MACEs). Kaplan-Meier method was used to estimate the survival rate, and multivariate Cox regression was used to analyze the relationship between RMRP and MACEs. RESULTS: The expression level of serum RMRP in patients with CAD was significantly higher than that in healthy people. Multivariate Logistic regression analysis showed that age, low-density lipoprotein cholesterol (LDL-C), RMRP and rest left ventricular ejection fraction (LVEF) were independent factors that affected SYNTAX scores. There were 19 cases of MACEs in the high RMRP group and 9 cases in the low RMRP group, and there was a significant difference in the MACE free survival curve between the two groups. Multivariate Cox regression analysis showed that age, SYNTAX score, rest LVEF and RMRP were risk factors for MACEs. CONCLUSIONS: Serum RMRP is a key factor affecting the degree of coronary artery disease and prognosis in CAD patients.

Combinational zimberelimab plus lenvatinib and chemotherapy for alpha-fetoprotein elevated, advanced gastric cancer patients (AFPGC): a phase 1 dose-escalation study.

BACKGROUND: Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was conducted to evaluate safety and efficacy of zimberelimab (GLS-010, anti-PD-1) plus lenvatinib and chemotherapy (XELOX) as the first-line treatment for AFPGC. METHODS: Histologically confirmed HER2-negative, advanced GC patients with elevated serum AFP level (≥ 20 ng/ml) were screened. Using a 3 + 3 dose escalation design, patients were administered varying doses of lenvatinib (12, 16, 20 mg) with GLS-010 and XELOX. The primary endpoints were safety and determination of recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and disease control rate. RESULTS: Nine patients were enrolled with no dose-limiting toxicities observed. Most frequent treatment-related AEs were fatigue (55.6%), hand-foot syndrome (55.6%) and rash (55.6%), and no grade ≥ 4 AEs were reported. All patients exhibited disease control with ORR reaching 33.3%. The median PFS and OS reached 7.67 months (95% CI 4.07-11.27) and 13.17 months (95% CI 2.78-23.56), respectively. Serum AFP level was found correlated with therapeutic responses. Further 16s rRNA sequencing analysis demonstrated altered gut microbiota with elevated abundance of Lachnospiraceae bacterium-GAM79 and Roseburia hominis A2-183. CONCLUSIONS: GLS-010 plus lenvatinib and XELOX demonstrated a manageable safety profile with promising efficacy for AFPGC. With RP2D of lenvatinib determined as 16 mg, further expansion cohort is now ongoing. Translational investigation suggested that serum AFP can be indictive for therapeutic responses and certain microbiota species indicating favorable responses to immunotherapy was elevated after the combinational treatment.

Evolutionary radiation strategy revealed in the Scarabaeidae with evidence of continuous spatiotemporal morphology and phylogenesis.

Evolutionary biology faces the important challenge of determining how to interpret the relationship between selection pressures and evolutionary radiation. The lack of morphological evidence on cross-species research adds to difficulty of this challenge. We proposed a new paradigm for evaluating the evolution of branches through changes in characters on continuous spatiotemporal scales, for better interpreting the impact of biotic/abiotic drivers on the evolutionary radiation. It reveals a causal link between morphological changes and selective pressures: consistent deformation signals for all tested characters on timeline, which provided strong support for the evolutionary hypothesis of relationship between scarabs and biotic/abiotic drivers; the evolutionary strategies under niche differentiation, which were manifested in the responsiveness degree of functional morphological characters with different selection pressure. This morphological information-driven integrative approach sheds light on the mechanism of macroevolution under different selection pressures and is applicable to more biodiversity research.

Erratum: Hypoxia induced exosomal circRNA promotes metastasis of Colorectal Cancer via targeting GEF-H1/RhoA axis: Erratum.

[This corrects the article DOI: 10.7150/thno.44419.].

MS/MS-based molecular networking discovery of sesquiterpenes from Carpesium abrotanoides L. with their cytotoxic and acetylcholinesterase inhibitory activity.

Employing an MS/MS-based molecular networking-guided strategy, three new eudesmane-type sesquiterpenes (1-3) and one undescribed pseudoguaianolide sesquiterpene (8), along with four known eudesmane-type sesquiterpene lactones (4-7) were extracted and purified from the herbs of Carpesium abrotanoides L. Structural elucidation encompassed comprehensive spectroscopic analysis, NMR calculations, DP4+ analysis, and ECD calculations. The cytotoxicity activity of all isolates was evaluated against two human hepatoma carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that compounds 2 and 4 showed moderate cytotoxic against HepG2 and Hep3B cells. Furthermore, all compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Particularly noteworthy is that, in comparison to the positive control, compound 1 demonstrated significant AChE inhibition with an inhibition rate of 77.86%. In addition, the inhibitory mechanism of compound 1 were investigated by in silico docking analyze and molecular dynamic simulation.

Chemotherapy re-use versus anti-angiogenic monotherapy as the third-line treatment of patients with metastatic colorectal cancer: a real-world cohort study.

BACKGROUND: There are various recommendations for third-line treatment in mCRC, however, there is no consensus on who is more suitable for particular strategy. Chemotherapy re-use in third-line setting is a common option in clinical practice. This study aimed to investigate the efficacy of third-line chemotherapy re-use by the comparison with that of anti-angiogenic monotherapy, and further find the population more suitable for third-line chemotherapy. METHODS: Using electronic medical records of patients with mCRC, a retrospective cohort study was conducted. A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting as control group were retrospectively collected. Baseline characteristics were analyzed using the χ² test or the Fisher's exact test. ROC curve and surv_cutpoint function of 'survminer' package in R software were used to calculate the cut-off value. Survival curves were plotted with the Kaplan-Meier method and were compared using the log-rank test. The Cox proportional hazard regression model was used to analyze the potential risk factors. RESULTS: A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting were retrospectively collected. Chemotherapy rechallenge was recorded in 93 patients (93/143, 65.0%), and the remaining patients chose new chemotherapeutic drugs that had not been previously used, including irinotecan-based (22/50), oxaliplatin-based (9/50), raltitrexed (9/50), gemcitabine (5/50) and other agents (5/50). The ORR and DCR of third-line chemotherapy reached 8.8%, 61.3%, respectively (anti-angiogenic monotherapy group: ORR 2.6%, DCR 47.4%). The mPFS and mOS of patients receiving chemotherapy were 4.9 and 12.0 m, respectively (anti-angiogenic monotherapy group: mPFS 2.7 m, mOS 5.2 m). Subgroup analyses found that patients with RAS/RAF mutation, longer PFS (greater than 10.6 m) in front-line treatment or larger tumor burden had better prognosis with third-line chemotherapy rather than anti-angiogenic monotherapy. CONCLUSIONS: Third-line chemotherapy re-use was effective in mCRC. Those with more aggressive characteristics (RAS/RAF mutant, larger tumor burden) or better efficacy of previous chemotherapy (longer PFS) were more appropriate for third-line chemotherapy, rather than anti-angiogenic monotherapy.

Hematuria after nocturnal exercise of a man: A case report.

BACKGROUND: A man experienced multiple episodes of macroscopic hematuria following nocturnal exercise. Urinary stones and tumors were considered the two most likely causes. The patient had two hobbies: Consuming health care products in large quantities and engaging in late-night running. CASE SUMMARY: Health care products contain a large amount of calcium phosphate, and we hypothesize that this could induce the formation of small phosphate stones. After exercise, the urinary system is abraded, resulting in bleeding. The patient was advised to stop using the health care products. Consequently, the aforementioned symptoms disappeared immediately. However, the patient resumed the above two habits one year later; correspondingly, the macroscopic hematuria reappeared. CONCLUSION: This finding further confirmed the above inference and allowed for a new avenue to determine the cause of the patient's hematuria.

Combined score based on plasma fibrinogen and platelet-lymphocyte ratio as a prognostic biomarker in esophageal squamous cell carcinoma.

BACKGROUND: Increasing evidence has showed that inflammatory biomarkers, including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and fibrinogen can be used as predictors in the prognosis of esophageal squamous cell carcinoma (ESCC). The aim of this study was to explore prognostic value of these biomarkers and evaluate the clinicopathological and prognostic significance of combined score based on plasma fibrinogen and platelet-lymphocyte ratio (F-PLR score). METHODS: A total of 506 patients with ESCC were enrolled in this study. Harrell's concordance index (c-index) was used to determine the optimal cut-off values of these markers and evaluate their prognostic significance. The relationship between factors with survival rates (including overall survival [OS] and disease-free survival [DFS]) was explored by Kaplan-Meier curve, univariate analysis and multivariate cox hazard analysis. RESULTS: Our result indicated that high F-PLR score was significantly associated with longer tumor length and deeper depth of tumor invasion (p < 0.01). The result of Cox multivariable analysis showed that F-PLR score was an independent prognostic factor for OS (p = 0.002) and DFS (p = 0.003). In addition, F-PLR score presented the greater c-index values for OS and DFS compared with NLR, PLR and fibrinogen level. Our result also showed that the c-index values for OS and DFS were both greater in TNM + F-PLR than those in TNM stage alone. CONCLUSIONS: In conclusion, F-PLR score is a predictive biomarker for prognosis in patients with ESCC.

Application of computer-aided diagnosis to predict malignancy in BI-RADS 3 breast lesions.

Purpose: To evaluate the ability of computer-aided diagnosis (CAD) system (S-Detect) to identify malignancy in ultrasound (US) -detected BI-RADS 3 breast lesions. Materials and methods: 148 patients with 148 breast lesions categorized as BI-RADS 3 were included in the study between January 2021 and September 2022. The malignancy rate, accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) were calculated. Results: In this study, 143 breast lesions were found to be benign, and 5 breast lesions were malignant (malignancy rate, 3.4 %, 95 % confidence interval (CI): 0.5-6.3). The malignancy rate rose significantly to 18.2 % (4/22, 95 % CI: 2.1-34.3) in the high-risk group with a "possibly malignant" CAD result (p = 0.017). With a "possibly benign" CAD result, the malignancy rate decreased to 0.8 % (1/126, 95 % CI: 0-2.2) in the low-risk group (p = 0.297). The AUC, sensitivity, specificity, accuracy, PPV, and NPV of the CAD system in BI-RADS 3 breast lesions were 0.837 (95 % CI: 77.7-89.6), 80.0 % (95 % CI: 73.6-86.4), 87.4 % (95 % CI: 82.0-92.7), 87.2 % (95 % CI: 81.8-92.6), 18.2 % (95 % CI: 2.1-34.3) and 99.2 % (95 % CI: 97.8-100.0), respectively. Conclusions: CAD system (S-Detect) enables radiologists to distinguish a high-risk group and a low-risk group among US-detected BI-RADS 3 breast lesions, so that patients in the low-risk group can receive follow-up without anxiety, while those in the high-risk group with a significantly increased malignancy rate should actively receive biopsy to avoid delayed diagnosis of breast cancer.

Designing and Evaluating a Portable UV-LED Vane Trap to Expedite Arthropod Biodiversity Discovery.

A novel design of a portable funnel light trap (PFLT) was presented for collecting insects in ecological studies. The trap consists of a compact plastic box equipped with a light source and power source, along with two plastic polypropylene interception vanes. The PFLT costs 18.3 USD per unit and weighs approximately 300 g. A maximum of six PFLT units can be packed in one medium-sized backpack (32 cm × 45 cm × 15 cm, 20 L), making it easier to set up multiple units in remote areas wherein biodiversity research is needed. The low cost and weight of the trap also allows for large-scale deployment. The design is customizable and can be easily manufactured to fit various research needs. To validate the PFLT's efficacy in collecting insects across different habitat types, a series of field experiments were conducted in South Korea and Laos, where 37 trials were carried out. The PFLT successfully collected 7497 insects without experiencing battery issues or damage by rain or wind. Insect compositions and abundances differed across the three sampled habitat types: forests, grasslands, and watersides. This new FLT trap is an important tool for studying and protecting insect biodiversity, particularly in areas wherein conventional light traps cannot be deployed.

Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial.

BACKGROUND: Anus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation. METHODS: This is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method. DISCUSSION: APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).

Decoding the roles of heat shock proteins in liver cancer.

Hepatocellular carcinoma (HCC) is one of the most common gastrointestinal malignancies, characterized by insidious onset and high propensity for metastasis and recurrence. Apart from surgical resection, there are no effective curative methods for HCC in recent years, due to resistance to radiotherapy and chemotherapy. Heat shock proteins (HSP) play a crucial role in maintaining cellular homeostasis and normal organism development as molecular chaperones for intracellular proteins. Both basic research and clinical data have shown that HSPs are crucial participants in the HCC microenvironment, as well as the occurrence, development, metastasis, and resistance to radiotherapy and chemotherapy in various malignancies, particularly liver cancer. This review aims to discuss the molecular mechanisms and potential clinical value of HSPs in HCC, which may provide new insights for HSP-based therapeutic interventions for HCC.

A highly oxidized germacranolide from elephantopus tomentosus inhibits the growth of hepatocellular carcinoma cells by targeting EGFR in vitro and in vivo.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high mortality and poor prognosis. WBDC-1 is a novel highly oxidized germacranolide from the Elephantopus tomentosus in our previous work, which has excellent anti-HCC activity, but the detailed mechanism is still unclear. In this study, we found that WBDC-1 was able to inhibit the proliferation and colony formation of Hep3B and HepG2 cells, as well as the cell migration ability and EMT. In addition, WBDC-1 showed no obvious toxicity to normal liver epithelial cells L-02. The potential targets of WBDC-1 were predicted by network pharmacology, and the following verified experiments showed that WBDC-1 exerted anti-HCC effect by targeting EGFR. Mechanismly, subsequent biological analysis showed that WBDC-1 can inhibit EGFR and its downstream RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways. Overexpression of EGFR reversed the anticancer properties of WBDC-1. Consistent with in vitro experiments, WBDC-1 was able to inhibit tumor growth and was non-toxic in xenograft tumor models. In summary, this study revealed a potential tumor suppressive mechanism of WBDC-1 and provided a novel strategy for HCC treatment. It also laid a foundation for further research on the anti-tumor effect of highly oxidized germacranolides.

[Retracted] Effects of miR­138­5p and miR­204­5p on the migration and proliferation of gastric cancer cells by targeting EGFR.

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that the numerous immunohistochemical images shown in Fig. 1D on p. 2626 exhibited a number of overlaps comparing among the data panels, such that data which were intended to show the results from differently performed experiments were likely to have been derived from a smaller number of original sources. A subsequent independent investigation of the data in this paper in the Editorial Office also revealed that certain of the cell migration and invasion assay data shown in Fig. 4A on p. 2629 were strikingly similar to data that had previously appeared in a couple of already published papers written by different authors at different research institutes.  Owing to the fact that the contentious data in Fig. 4 in the above article had already been published prior to its submission to Oncology Reports, in addition to the matter of several panels in Fig. 1D showing overlapping data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 2624-2634, 2018; DOI: 10.3892/or.2018.6389].

ALOX5 deficiency contributes to bladder cancer progression by mediating ferroptosis escape.

Ferroptosis is an iron-dependent form of regulated cell death driven by the lethal lipid peroxides. Previous studies have demonstrated that inducing ferroptosis holds great potential in cancer therapy, especially for patients with traditional therapy failure. However, cancer cells can acquire ferroptosis evasion during progression. To date, the therapeutic potential of inducing ferroptosis in bladder cancer (BCa) remains unclear, and whether a ferroptosis escape mechanism exists in BCa needs further investigation. This study verified that low pathological stage BCa cells were highly sensitive to RSL3-induced ferroptosis, whereas high pathological stage BCa cells exhibited obviously ferroptosis resistance. RNA-seq, RNAi-mediated loss-of-function, and CRISPR/Cas9 experiments demonstrated that ALOX5 deficiency was the crucial factor of BCa resistance to ferroptosis in vitro and in vivo. Mechanistically, we found that ALOX5 deficiency was regulated by EGR1 at the transcriptional level. Clinically, ALOX5 expression was decreased in BCa tissues, and its low expression was associated with poor survival. Collectively, this study uncovers a novel mechanism for BCa ferroptosis escape and proposes that ALOX5 may be a valuable therapeutic target and prognostic biomarker in BCa treatment.

First report on establishment and characterization of the extrahepatic cholangiocarcinoma sarcoma cell line CBC2T-2.

BACKGROUND: Extrahepatic cholangiocarcinoma sarcoma is extremely rare in clinical practice. These cells consist of both epithelial and mesenchymal cells. Patient-derived cell lines that maintain tumor characteristics are valuable tools for studying the molecular mechanisms associated with carcinosarcoma. However, cholangiocarcinoma sarcoma cell lines are not available in cell banks. AIM: To establish and characterize a new extrahepatic cholangiocarcinoma sarcoma cell line, namely CBC2T-2. METHODS: We conducted a short tandem repeat (STR) test to confirm the identity of the CBC2T-2 cell line. Furthermore, we assessed the migratory and invasive properties of the cells and performed clonogenicity assay to evaluate the ability of individual cells to form colonies. The tumorigenic potential of CBC2T-2 cells was tested in vivo using non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. The cells were injected subcutaneously and tumor formation was observed. In addition, immunohistochemical analysis was carried out to examine the expression of epithelial marker CK19 and mesenchymal marker vimentin in both CBC2T-2 cells and xenografts. The CBC2T-2 cell line was used to screen the potential therapeutic effects of various clinical agents in patients with cholangiocarcinoma sarcoma. Lastly, whole-exome sequencing was performed to identify genetic alterations and screen for somatic mutations in the CBC2T-2 cell line. RESULTS: The STR test showed that there was no cross-contamination and the results were identical to those of the original tissue. The cells showed round or oval-shaped epithelioid cells and mesenchymal cells with spindle-shaped or elongated morphology. The cells exhibited a high proliferation ratio with a doubling time of 47.11 h. This cell line has migratory, invasive, and clonogenic abilities. The chromosomes in the CBC2T-2 cells were polyploidy, with numbers ranging from 69 to 79. The subcutaneous tumorigenic assay confirmed the in vivo tumorigenic ability of CBC2T-2 cells in NOD/SCID mice. CBC2T-2 cells and xenografts were positive for both the epithelial marker, CK19, and the mesenchymal marker, vimentin. These results suggest that CBC2T-2 cells may have both epithelial and mesenchymal characteristics. The cells were also used to screen clinical agents in patients with cholangiocarcinoma sarcoma, and a combination of paclitaxel and gemcitabine was found to be the most effective treatment option. CONCLUSION: We established the first human cholangiocarcinoma sarcoma cell line, CBC2T-2, with stable biogenetic traits. This cell line, as a research model, has a high clinical value and would facilitate the understanding of the pathogenesis of cholangiocarcinoma sarcoma.

Phase Ib study of anti-EGFR antibody (SCT200) in combination with anti-PD-1 antibody (SCT-I10A) for patients with RAS/BRAF wild-type metastatic colorectal cancer.

OBJECTIVE: This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor (EGFR) antibody (SCT200) and an anti-programmed cell death 1 (PD-1) antibody (SCT-I10A) as third-line or subsequent therapies in patients with rat sarcoma viral oncogene (RAS)/v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (wt) metastatic colorectal cancer (mCRC). METHODS: We conducted a multicenter, open-label, phase Ib clinical trial. Patients with histologically confirmed RAS/BRAF wt mCRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200. The primary endpoints were the objective response rate (ORR) and safety. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-one patients were enrolled in the study through January 28, 2023. The ORR was 28.57% and the DCR was 85.71% (18/21). The median PFS and OS were 4.14 and 12.84 months, respectively. The treatment-related adverse events (TRAEs) were tolerable. Moreover, compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt mCRC in a third-line setting, no significant improvements in PFS and OS were observed in the combination group. CONCLUSIONS: SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt mCRC patients with an acceptable safety profile. Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting. (Registration No. NCT04229537).

Radix Salvia miltiorrhiza Ameliorates Burn Injuries by Reducing Inflammation and Promoting Wound Healing.

Purpose: Radix Salvia miltiorrhiza (RSM), a commonly used medicinal plant, has been reported to have anti-inflammatory effects, but relevant studies on burn injuries are lacking. We investigated the anti-inflammation and wound healing (WH) effects of an aqueous extract of RSM on a burn model in rats. Methods: The effects of RSM were studied by heat-induced burns in rats, treatment with vehicle, Jinwanhong ointment, and RSM (1.5 or 0.75 g/mL). Indicators of burn tissue (BT) were photographed by digital machines and analyzed. The microcirculation in BT was detected by scattered full-frame real-time imaging. Levels of inflammatory mediators and growth factors were measured by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining. Local pathologic changes in BT were observed by hematoxylin-and-eosin (HE) staining. Ultrahigh pressure liquid chromatography-linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap-MS) was used to explore the absorption of RSM in local skin, subcutaneous tissue, muscle tissue, serum, liver tissue, and kidney tissue. Results: RSM treatment could reduce the wound area, increase percent WH, increase blood perfusion in BT, reduce serum levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α (TNF-α), increase levels of epidermal growth factor (EGF), transforming growth factor (TGF)-ß, and hydroxyproline (Hyp) in serum, and increase protein expression of basic fibroblast growth factor (bFGF), TGF-ß1, EGF, and insulin-like growth factor-1 (IGF)-1 in skin tissues. RSM treatment led to micro-absorption in the skin, subcutaneous tissues, and muscle, but not in the blood, liver, or kidney. Conclusion: RSM may promote WH by exerting anti-inflammatory effects, improving local-wound microcirculation, and accelerating the metabolism at the wound surface.